title: Ginsenoside Rh1 eliminates the cytoprotective phenotype of human immunodeficiency virus type 1-transduced human macrophages by inhibiting the phosphorylation of pyruvate dehydrogenase lipoamide kinase isozyme 1.
abstract: Red ginseng (the steamed root of Panax ginseng C.A. MEYER, Araliaceae), which contains ginsenosides as its main constituents, is frequently used to treat tumor, inflammation, diabetes, stress and acquired immunodeficiency syndrome in Asian countries. Of these ginsenosides, only protopanaxadiol compound K has been reported to abolish the cytoprotective phenotype of human immunodeficiency virus type 1 (HIV-1)-transfected human macrophages. Here, we investigated the anti-cytoprotective effect of protopanaxatriol ginsenoside Rh1 on Tat-expressing cytoprotective CHME5 cells and D3-infected human primary macrophages. Treatment with ginsenoside Rh1 in the presence of lipopolysaccharide/cycloheximide (LPS/CHX) potently abolished the cytoprotective phenotype of Tat-transduced CHME5 cells as well as D3-infected human primary macrophages. Ginsenoside Rh1 significantly inhibited LPS/CHX-induced Akt phosphorylation, as well as mammalian target of rapamycin and Bcl-2-associated death promoter activation in both cell types. Furthermore, ginsenoside Rh1 inhibited pyruvate dehydrogenase lipoamide kinase isozyme 1 (PDK-1) phosphorylation. However, ginsenoside Rh1 did not inhibit phosphoinositide 3-kinase phosphorylation. Ginsenosides Rh1 in the presence of miltefosine (5 µM) additively increased the anti-cytoprotective activity against HIV-1 Tat-expressing macrophages. On the basis of these findings, we propose that ginsenoside Rh1 could possibly eliminate HIV-1 infected macrophages by inhibiting the PDK1/Akt pathway.
authors.affiliation: Department of Life and Nanopharmaceutical Sciences and Department of Pharmacy, Kyung Hee University, Seoul 130–701, South Korea.
authors.forename: Jin-Ju
authors.initials: JJ
authors.lastname: Jeong
authors.forename: Baek
authors.initials: B
authors.lastname: Kim
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects*; D036145:Ginsenosides / Q000302:isolation & purification / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000821:virology; D008856:Microscopy, Fluorescence; D005894:Panax / Q000737:chemistry; D010766:Phosphorylation; D018517:Plant Roots / Q000737:chemistry; D061251:Primary Cell Culture; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000096:biosynthesis
chemical_list: D036145:Ginsenosides; D008070:Lipopolysaccharides; C000631429:PDK1 protein, human; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D054322:tat Gene Products, Human Immunodeficiency Virus; C425564:ginsenoside Rh1; D003513:Cycloheximide; D017346:Protein Serine-Threonine Kinases